Human and mouse platelet transcriptomes and proteomes for phenotyping 3474 genes with hemostatic and platelet traits
Abstract: The hemostatic process relies on platelet and coagulation activation, with additional roles of red blood cells and the vessel wall. By systematic screening of databases for gene-linked information on hemostasis, we collected phenotypic profiles of 3474 orthologous human and mouse genes reg...
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Elsevier
2025-08-01
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| Series: | Blood Vessels, Thrombosis & Hemostasis |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2950327225000257 |
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| author | Jingnan Huang Federico Marini Fiorella A. Solari Frauke Swieringa Bas de Laat Ilaria De Simone Luigi Grassi Xiang Gui Kunpeng Li Elizabeth A. Middleton Neil V. Morgan Isabella Provenzale Carina Santos Saskia Schols Sarah Westbury Albert Sickmann Matthew T. Rondina Wolfram Ruf Mattia Frontini Johan W. M. Heemskerk |
| author_facet | Jingnan Huang Federico Marini Fiorella A. Solari Frauke Swieringa Bas de Laat Ilaria De Simone Luigi Grassi Xiang Gui Kunpeng Li Elizabeth A. Middleton Neil V. Morgan Isabella Provenzale Carina Santos Saskia Schols Sarah Westbury Albert Sickmann Matthew T. Rondina Wolfram Ruf Mattia Frontini Johan W. M. Heemskerk |
| author_sort | Jingnan Huang |
| collection | DOAJ |
| description | Abstract: The hemostatic process relies on platelet and coagulation activation, with additional roles of red blood cells and the vessel wall. By systematic screening of databases for gene-linked information on hemostasis, we collected phenotypic profiles of 3474 orthologous human and mouse genes regarding bleeding, arterial thrombosis, thrombophilia, platelet traits, coagulation, and erythrocytes. Comparisons showed that defects in 252 mouse genes led to increased bleeding combined with platelet dysfunction or thrombocytopenia, in addition to 150 human orthologs that are registered for familial bleeding disorders, based on panel sequencing. Additionally, 139 mouse genes contributed to arterial thrombosis without bleeding phenotype. To further investigate the role of platelets in hemostasis, we integrated multiple genome-wide RNA-sequencing transcriptomes and proteomes from healthy subjects and C57BL/6 mice. This provided reference levels for 54 790 (54 247) transcripts and 6379 (4563) proteins in human (mouse) platelets. Orthologous transcripts in human and mouse platelets correlated with R=0.75, whereas orthologous platelet proteins correlated with R=0.87. Comparison with the phenotypic analysis revealed the following: (i) overall high qualitative similarity of human and mouse platelets regarding composition and function; (ii) presence of transcripts in platelets for most of the 3474 phenotyped genes; (iii) preponderance of syndromic platelet-expressed genes; and (iv) 20-40% overlap with genes from genome-wide association studies. For 42 mouse genes, among which receptors, signaling proteins, and transcription regulators (ASXL1, ERG, GATA2, MEIS1, NFE2, and TAL1), we confirmed novel links with human platelet function or count. This interspecies comparison can serve as a valuable resource for researchers and clinicians studying the genetics of blood-borne hemostasis and thrombosis. |
| format | Article |
| id | doaj-art-d24cf4e0173548bd93bab93ebece980d |
| institution | Kabale University |
| issn | 2950-3272 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Blood Vessels, Thrombosis & Hemostasis |
| spelling | doaj-art-d24cf4e0173548bd93bab93ebece980d2025-08-20T03:25:08ZengElsevierBlood Vessels, Thrombosis & Hemostasis2950-32722025-08-012310006810.1016/j.bvth.2025.100068Human and mouse platelet transcriptomes and proteomes for phenotyping 3474 genes with hemostatic and platelet traitsJingnan Huang0Federico Marini1Fiorella A. Solari2Frauke Swieringa3Bas de Laat4Ilaria De Simone5Luigi Grassi6Xiang Gui7Kunpeng Li8Elizabeth A. Middleton9Neil V. Morgan10Isabella Provenzale11Carina Santos12Saskia Schols13Sarah Westbury14Albert Sickmann15Matthew T. Rondina16Wolfram Ruf17Mattia Frontini18Johan W. M. Heemskerk19Department of Biochemistry, Maastricht University, Maastricht, The Netherlands; Leibniz-Institut für Analytische Wissenschaften-ISAS-e.V., Dortmund, Germany; Department of Nephrology, The First Affiliated Hospital, Southern University of Science and Technology, Shenzhen, China; Correspondence: Jingnan Huang, Department of Nephrology, The First Affiliated Hospital, Southern University of Science and Technology, 1098 Xueyuan Blvd, Shenzhen, Guangdong 518071, China;Institute of Medical Biostatistics, Epidemiology and Informatics, Mainz, Germany; Center for Thrombosis and Hemostasis, University Medical Center, Johannes Gutenberg-University Mainz, Mainz, GermanyLeibniz-Institut für Analytische Wissenschaften-ISAS-e.V., Dortmund, GermanySynapse Research Institute Maastricht, Maastricht, The NetherlandsSynapse Research Institute Maastricht, Maastricht, The NetherlandsSynapse Research Institute Maastricht, Maastricht, The NetherlandsDepartment of Haematology, University of Cambridge, National Health Service Blood and Transplant, Cambridge, United KingdomSynapse Research Institute Maastricht, Maastricht, The NetherlandsDepartment of Nephrology, The First Affiliated Hospital, Southern University of Science and Technology, Shenzhen, ChinaMolecular Medicine Program, The University of Utah, Salt Lake City, UT; Division of Pulmonary and Critical Care Medicine, University of Utah School of Medicine, Salt Lake City, UTInstitute of Cardiovascular Sciences, University of Birmingham, Birmingham, United KingdomDepartment of Biochemistry, Maastricht University, Maastricht, The NetherlandsCenter for Thrombosis and Hemostasis, University Medical Center, Johannes Gutenberg-University Mainz, Mainz, GermanyDepartment of Hematology, Radboud University Medical Center, Nijmegen, The NetherlandsBristol Medical School, Faculty of Health and Life Sciences, University of Bristol, Bristol, United KingdomLeibniz-Institut für Analytische Wissenschaften-ISAS-e.V., Dortmund, Germany; Medizinische Fakultät, Medizinische Proteom-Center, Ruhr-Universität Bochum, Bochum, GermanyDivision of Pulmonary and Critical Care Medicine, University of Utah School of Medicine, Salt Lake City, UT; Departments of Medicine and Pathology, University of Utah Health and George Wahlen Department of Veterans Affairs Medical Center, Salt Lake City, UTCenter for Thrombosis and Hemostasis, University Medical Center, Johannes Gutenberg-University Mainz, Mainz, GermanyDepartment of Haematology, University of Cambridge, National Health Service Blood and Transplant, Cambridge, United Kingdom; Institute of Biomedical & Clinical Science, College of Medicine and Health, University of Exeter Medical School, Exeter, United KingdomDepartment of Biochemistry, Maastricht University, Maastricht, The Netherlands; Synapse Research Institute Maastricht, Maastricht, The Netherlands; Johan W. M. Heemskerk, Synapse Research Institute, Koningin Emmaplein 7, 6217 KD Maastricht, The Netherlands;Abstract: The hemostatic process relies on platelet and coagulation activation, with additional roles of red blood cells and the vessel wall. By systematic screening of databases for gene-linked information on hemostasis, we collected phenotypic profiles of 3474 orthologous human and mouse genes regarding bleeding, arterial thrombosis, thrombophilia, platelet traits, coagulation, and erythrocytes. Comparisons showed that defects in 252 mouse genes led to increased bleeding combined with platelet dysfunction or thrombocytopenia, in addition to 150 human orthologs that are registered for familial bleeding disorders, based on panel sequencing. Additionally, 139 mouse genes contributed to arterial thrombosis without bleeding phenotype. To further investigate the role of platelets in hemostasis, we integrated multiple genome-wide RNA-sequencing transcriptomes and proteomes from healthy subjects and C57BL/6 mice. This provided reference levels for 54 790 (54 247) transcripts and 6379 (4563) proteins in human (mouse) platelets. Orthologous transcripts in human and mouse platelets correlated with R=0.75, whereas orthologous platelet proteins correlated with R=0.87. Comparison with the phenotypic analysis revealed the following: (i) overall high qualitative similarity of human and mouse platelets regarding composition and function; (ii) presence of transcripts in platelets for most of the 3474 phenotyped genes; (iii) preponderance of syndromic platelet-expressed genes; and (iv) 20-40% overlap with genes from genome-wide association studies. For 42 mouse genes, among which receptors, signaling proteins, and transcription regulators (ASXL1, ERG, GATA2, MEIS1, NFE2, and TAL1), we confirmed novel links with human platelet function or count. This interspecies comparison can serve as a valuable resource for researchers and clinicians studying the genetics of blood-borne hemostasis and thrombosis.http://www.sciencedirect.com/science/article/pii/S2950327225000257 |
| spellingShingle | Jingnan Huang Federico Marini Fiorella A. Solari Frauke Swieringa Bas de Laat Ilaria De Simone Luigi Grassi Xiang Gui Kunpeng Li Elizabeth A. Middleton Neil V. Morgan Isabella Provenzale Carina Santos Saskia Schols Sarah Westbury Albert Sickmann Matthew T. Rondina Wolfram Ruf Mattia Frontini Johan W. M. Heemskerk Human and mouse platelet transcriptomes and proteomes for phenotyping 3474 genes with hemostatic and platelet traits Blood Vessels, Thrombosis & Hemostasis |
| title | Human and mouse platelet transcriptomes and proteomes for phenotyping 3474 genes with hemostatic and platelet traits |
| title_full | Human and mouse platelet transcriptomes and proteomes for phenotyping 3474 genes with hemostatic and platelet traits |
| title_fullStr | Human and mouse platelet transcriptomes and proteomes for phenotyping 3474 genes with hemostatic and platelet traits |
| title_full_unstemmed | Human and mouse platelet transcriptomes and proteomes for phenotyping 3474 genes with hemostatic and platelet traits |
| title_short | Human and mouse platelet transcriptomes and proteomes for phenotyping 3474 genes with hemostatic and platelet traits |
| title_sort | human and mouse platelet transcriptomes and proteomes for phenotyping 3474 genes with hemostatic and platelet traits |
| url | http://www.sciencedirect.com/science/article/pii/S2950327225000257 |
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